P974: INTERIM ANALYSIS OF THE LAUNCH STUDY-A MULTICENTER, OPEN-LABEL STUDY OF SELINEXOR, DEXAMETHASONE PLUS CHEMOTHERAPY DRUGS IN RELAPSED/ REFRACTORY MULTIPLE MYELOMA
Authors: Chunyan Sun, Baijun Fang, Guangxun Gao, Ai‑li He, Fei Zhao, Junying LI, Chun Zhang, Weiming LI, Hui Cheng, Huili Cai, Bin Chen, Jingming Guo, Yu Hu
Journal: HemaSphere (2023)

Topic: 14. Myeloma and other monoclonal gammopathies - Clinical Background: Exportin 1 (XPO1) participates the nuclear export of tumor suppressor proteins (TSPs), is associated with poor prognosis and drug resistance (PI or IMiD) in MM. Selinexor is a novel, oral, first-in-class selective inhibitor of XPO1. In STORM study, selinexor (80mg biweekly) plus dexamethasone (20mg biweekly) (Xd) have demonstrated activity against relapsed/refractory multiple myeloma. In pre-clinical studies, selinexor played a synergistic anti-tumor role with chemotherapy drugs, but there is still a lack of clinical data on combined treatment. Aims: To assess the preliminary efficacy, safety, and tolerability of the combination of Xd plus chemotherapy drugs in pts with RRMM. Methods: The LAUNCH study is a multicenter, open-label study (NCT04877275) enrolled patients with relapsed/refractory MM who had at least one prior treatment. There are two arms in this study, and 25 patients will be enrolled in each arm. XDd Arm: Selinexor 80mg d1,8,15,22, Dexamethasone 40mg d1,8,15,22, and Liposome Doxorubicin 25mg/m2 d1; XCd Arm: Selinexor 100mg d1,8,15,22, Dexamethasone 40mg d1,8,15,22, and Cyclophosphamide 300mg/m2 d1,8,15,22. 28d per cycle in both arms. Results: As of Feb 24th 2023, 28 patients were enrolled (18 in XDd and 10 in XCd). Of these, 11 patients were male and 17 were female. The median age was 57 years (range: 43-74 years). The median time since initial diagnosis was 3.3 years (range: 0.5-15 years). The median number of prior treatments was 3 (range: 1– 7). There were 8 patients (28.6%) with high-risk cytogenetic abnormalities, 6 patients (21.4%) with extramedullary disease (EMD). 4 patients (14.3%) received prior autologous stem cell transplantation and 3 patients (10.7%) received CAR-T therapy. 27 of 28 patients (96.4%) were exposed to bortezomib, 23 patients (82.1%) were exposed to lenalidomide, 9 patients (32.1%) exposed to pomalidomide, 5 patients (15%) exposed to daratumumab. 4 patients (20%) exposed to cyclophosphamide and liposome doxorubicin. The median treatment time of all patients was 16 weeks (range: 1-48weeks). 8 patients still remained on treatment. 22 patients were evaluated for efficacy. The ORR was 54.5% (56.3% in 16 XDd arm and 50% in 6 XCd arm) including 1 VGPR and 13 PRs. 7 patients had stable disease. The most common hematological adverse events (All Grades, Grade ≥3) were thrombocytopenia (67.9%, 28.6%), leukopenia (57.1%, 28.6%), and anemia (50%, 28.6%). The most common non-hematological adverse events (All Grades, Grade ≥3) were nausea (64.3%, 3.6%), vomiting (50%, 7.1%) and fatigue (50%, 3.6%). Most treatment related adverse events were observed in the first 8 weeks and were alleviated over time. Summary/Conclusion: Once weekly selinexor and dexamethasone (Xd) combined with cyclophosphamide or liposome doxorubicin showed encouraging efficacy in relapsed/refractory MM. It also well-tolerated and no new safety signal was identified. Keywords: Chemotherapy, Multiple myeloma, Refractory, Relapse